At the end of April, I had the opportunity to attend the annual meeting of the American Academy of Neurology (AAN) – the largest annual neurological congress where more than 10,000 neurologists and neuroscientists meet. Of course, multiple sclerosis was again in focus, and many lectures and posters dealt with new therapies and new strategies for treating the disease. Interesting was the presentation of the data from the INFORMS study. I had already reported on this study once in this blog. In this study, the effect of Fingolimod (Gilenya®) against placebo in primary chronic progressive MS (PPMS) was tested. As early as a press release at the end of 2014, it was announced that Fingolimod had no effect on disease progression in PPMS. The study results now presented visualized this negative result once again very impressively. There was absolutely no difference between a placebo treatment and the verum treatment. The curves were almost identical, even when using a compound parameter from EDSS and MSFC, which could expect an even better capture of disease progression.
Surprisingly, however, Fingolimod had a highly significant effect on the suppression of inflammatory activity in MRI – without this effect having an impact on the clinical course. This is an extremely important finding: It can be deduced from this that sole anti-inflammatory action in the late, progressive phases of an MS has no significant influence. Whether one should therefore completely abandon an anti-inflammatory therapy in these disease phases is another question. But it seems clear, as Fred Lublin, who presented the study results, put it succinctly: “We need completely new concepts for chronic progressive MS”.
High-dose biotin
Interestingly, a completely new concept for the treatment of chronic MS was then presented a little later, which has surprised many. French researchers have examined the effect of high-dose biotin (300 mg/d) on the course of progressive MS. Biotin is a water-soluble vitamin that acts as a coenzyme for carboxylases at key steps in energy metabolism and fatty acid synthesis. Among other things, biotin activates the acetyl-CoA-carboxylase, a potential key enzyme of myelin synthesis. According to the German Society for Nutrition, 30-60 μg per day are considered an estimate for the appropriate biotin intake in healthy adults. The dose studied is thus 10,000 times higher. In the study, 154 patients received either 300 mg/d biotin orally (n = 103) or placebo (n = 51). The average disease duration was 16.6 years, 41% suffered from primary and 59% from secondary progressive MS. The patients were on average 51.4 years old and had a mean EDSS value of 6.1. The patients must have had a disability progression of at least 1.0 EDSS points in the past two years. Existing therapies with MS drugs were maintained. The primary endpoint was defined as the proportion of patients with an improvement in the EDSS score after nine months, which also existed after twelve months – so a relatively strong endpoint definition. This primary endpoint was reached by 12.6% of the patients in the biotin group, while no patient in the placebo group achieved this (p = 0.005). The primary endpoint was achieved to 77% via the improvement of the EDSS value and to 39% via the 7.6 m walking distance. The side effect profile of the study groups showed no significant differences, except for low thyroid values in the treatment group. So overall a surprising and encouraging result, which will certainly trigger further study activities. It remains to be seen whether this result can be reproduced. In any case, this presentation was one of the most interesting events of this year’s Academy.
